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Summary of Background Data. CEPs play a vital role in progression of intervertebral disc degenerative diseases. However, the ideal and economic therapies for CEPs degeneration are still urgently required.

Results. Compared with normal CEP, level of α2 M was slightly increased in CEP from degenerative patients, whereas MMP-13 was sharply elevated. In vitro, α2 M inhibited expression and activity of MMP-3 or MMP-13 in a dose-dependent manner in rat CEP cells stimulated by TNF-α. The α2 M refrained phosphorylation of IκBα and inhibited nuclear translocation of p65. Finally, supplemental α2 M reduced expression of MMP-13, and promoted expression of Sox9, aggrecan, and type II collagen in CEP area of ex vivo IVDs cultured with TNF-α.

Conclusion. α2 M is not sufficiently produced to inactivate higher concentrations of catabolic factor MMP-13 found in the degenerated CEP. Supplemental α2 M protects against the progression of IVD degeneration by inhibiting effects of proinflammatory cytokines.

Level of Evidence: N/A

The features of human CEP degeneration with increased catabolic factors and decreased anabolic factors are verified. CEP cells treated by TNF-α compared with IL-1β show more effective degeneration. Alpha 2-macroglobulin can suppress TNF-α-induced activation of NF-кB signaling pathway in CEP cells, thus alleviating the degeneration of IVD.

∗Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

BH and JC contributed to this work equally and should be regarded as the cofirst author.

The manuscript submitted does not contain information about medical device(s)/drug(s).

National Science Foundation of China (81672208) and Medical and health research project of Zhejiang Province (2015KYB448), and Zhejiang Medical Science and Technology project (2016138375) funds were received in support of this work.